Mingjie Li, MD, PhD
Dr. Li is a Research Assistant Professor in the Viral Vectors Core at the Hope Center for Neurological Disorders. Gene delivery to nervous tissues is not only important for neuroscience research but also a potential means for the treatment of neurological disorders. However, most cell types relevant to nervous system disorders are difficult to transfect using non-viral transfection and traditional viral transduction methods. Genetic manipulation of brain cells in vivo has been even more challenging. Lentiviral vectors are able to transduce non-dividing cells, including neurons, making them attractive vehicles for gene delivery to neural cells. Several adeno-associated virus (AAV) serotypes have also been shown to successfully transduce cultured neurons and to mediate robust transgene expression in the brain.
We are developing new vectors for neurological applications. The goal of the Viral Vectors Core is to assist Washington University neuroscience researchers in the design and production of various kinds of vectors. Currently, we are focused on lentiviral and AAV vectors for use in cell culture and in vivo pre-clinical experiments designed to understand the causes and treatments for nervous system disorders. Among the projects we now undertaking are developing tissue-specific expression vectors and incorporating viral vectors with RNAi technology. We will also aim to promote translation of preclinical research findings into clinical applications.
Dr. Li received an M.D. from Jiamusi Medical College, China in 1983 and a Ph.D. from Kochi Medical School, Japan in 1994. He worked at Yale University studying immunoglobulin gene recombination and subsequently at the Beckman Research Institute of the City of Hope, California studying viral vector delivery of therapeutic genes against HIV infection before joining the Neurology Department at Washington University as an Assistant Research Professor in April, 2006.
Li, M. & Rossi, J.J. Lentiviral vector delivery of siRNA and shRNA encoding genes into cultured and primary hematopoietic cells. Methods in molecular biology (Clifton, N.J 433, 287-299 (2008).
Anderson, J., Li, M.J., Palmer, B., Remling, L., Li, S., Yam, P., Yee, J.K., Rossi, J., Zaia, J. & Akkina, R. Safety and efficacy of a lentiviral vector containing three anti-HIV genes--CCR5 ribozyme, tat-rev siRNA, and TAR decoy--in SCID-hu mouse-derived T cells. Mol Ther 15, 1182-1188 (2007).
Li, M.-J. & Rossi, J. Lentivirus transduction of hematopoietic cells. in Gene transfer: Delivery and expression of DNA and RNA (eds. Friedmann, T. & Rossi, J.) 75-82 (Cold Spring Harbor Labratory Press, Cold Spring Harbor, NY, 2007).
Robbins, M.A., Li, M., Leung, I., Li, H., Boyer, D.V., Song, Y., Behlke, M.A. & Rossi, J.J. Stable expression of shRNAs in human CD34+ progenitor cells can avoid induction of interferon responses to siRNAs in vitro. Nat Biotechnol 24, 566-571 (2006).
Li, M., Li, H. & Rossi, J.J. RNAi in combination with a ribozyme and TAR decoy for treatment of HIV infection in hematopoietic cell gene therapy. Ann N Y Acad Sci 1082, 172-179 (2006).
Unwalla, H.J., Li, H.T., Bahner, I., Li, M.J., Kohn, D. & Rossi, J.J. Novel Pol II fusion promoter directs human immunodeficiency virus type 1-inducible coexpression of a short hairpin RNA and protein. Journal of virology 80, 1863-1873 (2006).
Li, M.J., Kim, J., Li, S., Zaia, J., Yee, J.K., Anderson, J., Akkina, R. & Rossi, J.J. Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther 12, 900-909 (2005).
Li, M. & Rossi, J.J. Lentiviral vector delivery of siRNA and shRNA encoding genes into cultured and primary hematopoietic cells. Methods in molecular biology (Clifton, N.J 309, 261-272 (2005).
Castanotto, D., Tommasi, S., Li, M., Li, H., Yanow, S., Pfeifer, G.P. & Rossi, J.J. Short hairpin RNA-directed cytosine (CpG) methylation of the RASSF1A gene promoter in HeLa cells. Mol Ther 12, 179-183 (2005).
Cook, H.L., Lytle, J.R., Mischo, H.E., Li, M.J., Rossi, J.J., Silva, D.P., Desrosiers, R.C. & Steitz, J.A. Small nuclear RNAs encoded by Herpesvirus saimiri upregulate the expression of genes linked to T cell activation in virally transformed T cells. Curr Biol 15, 974-979 (2005).
Li, M.J. & Rossi, J.J. Lentiviral vector delivery of recombinant small interfering RNA expression cassettes. Methods Enzymol 392, 218-226 (2005).
Banerjea, A., Li, M.J., Remling, L., Rossi, J. & Akkina, R. Lentiviral transduction of Tar Decoy and CCR5 ribozyme into CD34+ progenitor cells and derivation of HIV-1 resistant T cells and macrophages. AIDS Res Ther 1, 2 (2004).
Unwalla, H.J., Li, M.J., Kim, J.D., Li, H.T., Ehsani, A., Alluin, J. & Rossi, J.J. Negative feedback inhibition of HIV-1 by TAT-inducible expression of siRNA. Nat Biotechnol 22, 1573-1578 (2004).
Li, M.J., McMahon, R., Snyder, D.S., Yee, J.K. & Rossi, J.J. Specific killing of Ph+ chronic myeloid leukemia cells by a lentiviral vector-delivered anti-bcr/abl small hairpin RNA. Oligonucleotides 13, 401-409 (2003).
Akkina, R., Banerjea, A., Bai, J., Anderson, J., Li, M.J. & Rossi, J. siRNAs, ribozymes and RNA decoys in modeling stem cell-based gene therapy for HIV/AIDS. Anticancer Res 23, 1997-2005 (2003).
Banerjea, A., Li, M.J., Bauer, G., Remling, L., Lee, N.S., Rossi, J. & Akkina, R. Inhibition of HIV-1 by lentiviral vector-transduced siRNAs in T lymphocytes differentiated in SCID-hu mice and CD34+ progenitor cell-derived macrophages. Mol Ther 8, 62-71 (2003).
Li, M.J., Bauer, G., Michienzi, A., Yee, J.K., Lee, N.S., Kim, J., Li, S., Castanotto, D., Zaia, J. & Rossi, J.J. Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs. Mol Ther 8, 196-206 (2003).
Lee, N.S., Dohjima, T., Bauer, G., Li, H., Li, M.J., Ehsani, A., Salvaterra, P. & Rossi, J. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol 20, 500-505 (2002).
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